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Endocrine Disruptor Chemicals and Estrogenic Activity in the Context of Health Risk Assessment

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A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601). This special issue belongs to the section "Environmental Health".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 31522

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Prof. Dr. Tiziana Schilirò

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Guest Editor

Department of Public Health and Pediatrics, University of Torino, Piazza Polonia 94, 10126 Torino, Italy
Interests: endocrine disruptors; estrogenic activity; E-screen; gene reporter assay; particulate matter; air pollution; PM10; PM2.5; biomonitoring; effect based monitoring tools; mutagenicity; genotoxicity; comet assay; Ames test; risk assessment; health risk assessment

Dr. Giovanna Di Nardo

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Department of Life Sciences and Systems Biology, University of Torino, 10123 Torino, Italy
Interests: aromatase; cytochromes P450; steroid hormones; endocrine disrupting chemicals
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Dr. Cinzia La Rocca

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Guest Editor

Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
Interests: chemical health effects; plasticizers; biomarkers; endocrine disrupting chemicals; contaminants; human biomonitoring; exposure and health
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Prof. Dr. Giovanna Cristina Varese

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Department of Life Sciences and Systems Biology (DBIOS), University of Turin, Viale Mattioli 25, 10125 Turin, Italy
Interests: fungal diversity; preservation and valorization; fungal ecology; microbial biobanks; microbiomes
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Special Issue Information

Dear Colleagues,

The World Health Organization defines endocrine-disrupting chemicals (EDCs) as “exogenous substances or mixtures that alter function(s) of the endocrine system and consequently cause adverse health effects in an intact organism, or its progeny, or (sub) populations”. EDCs are a highly heterogeneous group of natural and synthesized chemicals, which are ubiquitous in the environment. Human exposure to them occurs through different ways, such as inhalation, ingestion of contaminated food and/or water, and dermal contact by the use of personal care products.

EDCs can alter the functions of different natural hormones; they can act directly on hormone receptors as agonists or as antagonists or indirectly interfering with synthesis, transport, metabolism, and excretion of hormones. Exposure to low doses of EDCs is enough to induce effects, and the exposure during specific life time periods can induce permanent adverse effects.

Traditional assessment of EDCs, based on identifying and quantifying individual chemicals, has some limitations: it is performed considering specific known substances and cannot quantify the effect of unknown or unconsidered compounds, and the cumulative effects of a mixture cannot be directly concluded from individual EDC levels as synergistic/antagonistic interactions are not considered. In addition to the chemical assessment, biological monitoring represents a key element. It is performed through effect-based tools which are able to evaluate the total effect induced by numerous, bioavailable chemicals with the same mechanism of action. In particular, the estrogenic activity of environmental or biological samples has been proposed and utilized as an EDC exposure biomarker.

Prof. Tiziana Schilirò
Dr. Giovanna Di Nardo
Dr. Cinzia La Rocca
Prof. Giovanna Cristina Varese
Guest Editors

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Keywords

EDCs
Endocrine-disrupting compounds
Estrogenic activity
Biomarkers
Low-dose exposure
Environmental risk assessment
Health risk assessment

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Published Papers (7 papers)

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Research

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12 pages, 2112 KiB

Open AccessArticle

Microbial Polymers as Sustainable Agents for Mitigating Health Risks of Plant-Based Endocrine Disruptors in Surface Water

by Moushumi Ghosh, Krishnaswamy Balamurugan and Vivek Sharma

Int. J. Environ. Res. Public Health 2021, 18(19), 10040; https://doi.org/10.3390/ijerph181910040 - 24 Sep 2021

Cited by 2 | Viewed by 1794

Abstract

This study investigated the binding abilities of extracellular polymers produced by an environmentally isolated strain of Enterococcus hirae towards phytoestrogen endocrine disruptors—biochanin A, formonetin, genistein and daidzein. The extracellular biopolymer exhibited notable binding and removal for all four phytoestrogens, with a maximum removal of daidzein (87%) followed by genistein (72%) at a 1–1.5 mg/mL concentration. Adsorption proceeded rapidly at ambient temperature. The adsorption data fitted well with the Langmuir isotherm. Based on the adsorption energy, the biopolymer binding of phytoestrogens was inferred as daidzein > genistein > biochanin A > formononetin. Toxicity of the biopolymer (5–250 µg/mL) evaluated using RAW 264.7 cell lines indicated no significant (p < 0.05) changes in viability. In biopolymer-challenged Caenorhabditis elegans previously exposed to daidzein, complete protection to developmental toxicity, such as reduced egg-laying capacity, egg viability and progeny counts of the worm, was observed. The results of this study offer valuable insights into understanding the potential role of microbial extracellular biopolymers in binding and removal of phytoestrogens with sustainable technological implications in modulating the toxic effect of high levels of endocrine disruptors in the environment. Full article

(This article belongs to the Special Issue Endocrine Disruptor Chemicals and Estrogenic Activity in the Context of Health Risk Assessment)

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16 pages, 395 KiB

Open AccessArticle

Lifestyle Habits and Exposure to BPA and Phthalates in Women of Childbearing Age from Northern Italy: A Pilot Study

by Ilaria Di Napoli, Sara Tagliaferri, Eduardo Sommella, Emanuela Salviati, Debora Porri, Benedetta Raspini, Hellas Cena, Pietro Campiglia, Cinzia La Rocca, Rosa Maria Cerbo and Rachele De Giuseppe

Int. J. Environ. Res. Public Health 2021, 18(18), 9710; https://doi.org/10.3390/ijerph18189710 - 15 Sep 2021

Cited by 13 | Viewed by 3226

Abstract

Background: Endocrine-disrupting chemicals (EDCs) are compounds that interfere with aspects of hormonal signaling. Considerable attention has been paid to their biological effects especially in women of childbearing age or during pregnancy as EDCs have been reported to cross the placenta becoming concentrated in the fetus’ circulation. Lifestyle habits, daily consumption of packaged foods and use of healthcare/cosmetic products are associated with increased EDCs levels. This cross-sectional research examined the EDCs levels and the lifestyle determinants of EDC exposure in a cohort of reproductive-age women from Northern Italy. Methods: Forty-five women (median age: 36, IQR: 30–38) were evaluated for urinary bisphenol A (BPA) and phthalates levels and also studied for EDCs’ major determinants of daily exposure; food frequency/dietary, physical activity, smoking habits and weight status. Results: Although 100% of women seemed to have been exposed to common sources of EDCs, they reported a healthy lifestyle. The multivariable model described a positive and significant association between consumption of sauces/dressings in plastic containers and monoethyl phthalate exposure (p = 0.037). Conclusions: Since reproductive age encompasses a critical window for future health and functioning of the “mothers-to-be” and their children, future studies on prenatal dietary BPA and phthalate exposure and the role of consumer product choices in reducing such exposure are recommended. Full article

(This article belongs to the Special Issue Endocrine Disruptor Chemicals and Estrogenic Activity in the Context of Health Risk Assessment)

13 pages, 3683 KiB

Open AccessArticle

Development of a Human Estrogen Receptor Dimerization Assay for the Estrogenic Endocrine-Disrupting Chemicals Using Bioluminescence Resonance Energy Transfer

by Hye Mi Kim, Hyeyeong Seo, Yooheon Park, Hee-Seok Lee, Seok-Hee Lee and Kwang Suk Ko

Int. J. Environ. Res. Public Health 2021, 18(16), 8875; https://doi.org/10.3390/ijerph18168875 - 23 Aug 2021

Cited by 6 | Viewed by 3133

Abstract

Endocrine-disrupting chemicals (EDCs) are found in food and various other substances, including pesticides and plastics. EDCs are easily absorbed into the body and have the ability to mimic or block hormone function. The radioligand binding assay based on the estrogen receptors binding affinity is widely used to detect estrogenic EDCs but is limited to radioactive substances and requires specific conditions. As an alternative, we developed a human cell-based dimerization assay for detecting EDC-mediated ER-alpha (ERα) dimerization using bioluminescence resonance energy transfer (BRET). The resultant novel BRET-based on the ERα dimerization assay was used to identify the binding affinity of 17β-estradiol (E2), 17α-estradiol, corticosterone, diethylhexyl phthalate, bisphenol A, and 4-nonylphenol with ERα by measuring the corresponding BRET signals. Consequently, the BRET signals from five chemicals except corticosterone showed a dose-dependent sigmoidal curve for ERα, and these chemicals were suggested as positive chemicals for ERα. In contrast, corticosterone, which induced a BRET signal comparable to that of the vehicle control, was suggested as a negative chemical for ERα. Therefore, these results were consistent with the results of the existing binding assay for ERα and suggested that a novel BRET system can provide information about EDCs-mediated dimerization to ERα. Full article

(This article belongs to the Special Issue Endocrine Disruptor Chemicals and Estrogenic Activity in the Context of Health Risk Assessment)

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18 pages, 3415 KiB

Open AccessArticle

Molecular Basis for Endocrine Disruption by Pesticides Targeting Aromatase and Estrogen Receptor

by Chao Zhang, Tiziana Schilirò, Marta Gea, Silvia Bianchi, Angelo Spinello, Alessandra Magistrato, Gianfranco Gilardi and Giovanna Di Nardo

Int. J. Environ. Res. Public Health 2020, 17(16), 5664; https://doi.org/10.3390/ijerph17165664 - 5 Aug 2020

Cited by 41 | Viewed by 10958

Abstract

The intensive use of pesticides has led to their increasing presence in water, soil, and agricultural products. Mounting evidence indicates that some pesticides may be endocrine disrupting chemicals (EDCs), being therefore harmful for the human health and the environment. In this study, three pesticides, glyphosate, thiacloprid, and imidacloprid, were tested for their ability to interfere with estrogen biosynthesis and/or signaling, to evaluate their potential action as EDCs. Among the tested compounds, only glyphosate inhibited aromatase activity (up to 30%) via a non-competitive inhibition or a mixed inhibition mechanism depending on the concentration applied. Then, the ability of the three pesticides to induce an estrogenic activity was tested in MELN cells. When compared to 17β-estradiol, thiacloprid and imidacloprid induced an estrogenic activity at the highest concentrations tested with a relative potency of 5.4 × 10⁻¹⁰ and 3.7 × 10⁻⁹, respectively. Molecular dynamics and docking simulations predicted the potential binding sites and the binding mode of the three pesticides on the structure of the two key targets, providing a rational for their mechanism as EDCs. The results demonstrate that the three pesticides are potential EDCs as glyphosate acts as an aromatase inhibitor, whereas imidacloprid and thiacloprid can interfere with estrogen induced signaling. Full article

(This article belongs to the Special Issue Endocrine Disruptor Chemicals and Estrogenic Activity in the Context of Health Risk Assessment)

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19 pages, 615 KiB

Open AccessArticle

Cross-Sectional and Longitudinal Effects of PCB Exposure on Human Stress Hormones in the German HELPcB Surveillance Program

by Petra Maria Gaum, Viktoria Stefanie Vida, Thomas Schettgen, André Esser, Thomas Kraus, Monika Gube and Jessica Lang

Int. J. Environ. Res. Public Health 2020, 17(13), 4708; https://doi.org/10.3390/ijerph17134708 - 30 Jun 2020

Cited by 2 | Viewed by 2283

Abstract

Multiple pathological associations are attributed to PCBs (polychlorinated biphenyls). Research shows a positive association of PCBs with dehydroepiandrosterone sulfate (DHEAS) concentration but the results on the stress hormone cortisol have been inconsistent so far. This study is the first to examine not only the cross-sectional but also the longitudinal effects of PCB exposure on the stress hormones DHEAS and cortisol. Over a period of three years, 112 former employees occupationally exposed to PCBs were tested for their body burden with different types of PCBs (lower and higher chlorinated, dioxin-like and hydroxylated) and for their stress hormone concentration. Highly exposed employees showed a significantly higher risk for higher DHEAS values. Multiple linear regression analysis revealed a positive relationship between the exposure to lower chlorinated PCBs and DHEAS. Mixed models also revealed a significantly positive correlation between lower chlorinated PCBs with DHEAS when controlled for a cross-section. However, an effect for cortisol was not found. These results suggest a causal pathophysiological relationship between PCB exposure and DHEAS concentration, but not with cortisol. The health consequences of high DHEAS concentrations are discussed. Full article

(This article belongs to the Special Issue Endocrine Disruptor Chemicals and Estrogenic Activity in the Context of Health Risk Assessment)

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24 pages, 659 KiB

Open AccessReview

Integrated Genomic and Bioinformatics Approaches to Identify Molecular Links between Endocrine Disruptors and Adverse Outcomes

by Jacopo Umberto Verga, Matthew Huff, Diarmuid Owens, Bethany J. Wolf and Gary Hardiman

Int. J. Environ. Res. Public Health 2022, 19(1), 574; https://doi.org/10.3390/ijerph19010574 - 5 Jan 2022

Cited by 6 | Viewed by 3844

Abstract

Exposure to Endocrine Disrupting Chemicals (EDC) has been linked with several adverse outcomes. In this review, we examine EDCs that are pervasive in the environment and are of concern in the context of human, animal, and environmental health. We explore the consequences of EDC exposure on aquatic life, terrestrial animals, and humans. We focus on the exploitation of genomics technologies and in particular whole transcriptome sequencing. Genome-wide analyses using RNAseq provides snap shots of cellular, tissue and whole organism transcriptomes under normal physiological and EDC perturbed conditions. A global view of gene expression provides highly valuable information as it uncovers gene families or more specifically, pathways that are affected by EDC exposures, but also reveals those that are unaffected. Hypotheses about genes with unknown functions can also be formed by comparison of their expression levels with genes of known function. Risk assessment strategies leveraging genomic technologies and the development of toxicology databases are explored. Finally, we review how the Adverse Outcome Pathway (AOP) has exploited this high throughput data to provide a framework for toxicology studies. Full article

(This article belongs to the Special Issue Endocrine Disruptor Chemicals and Estrogenic Activity in the Context of Health Risk Assessment)

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18 pages, 1620 KiB

Open AccessReview

Combined Effects of Different Endocrine-Disrupting Chemicals (EDCs) on Prostate Gland

by Maria De Falco and Vincenza Laforgia

Int. J. Environ. Res. Public Health 2021, 18(18), 9772; https://doi.org/10.3390/ijerph18189772 - 16 Sep 2021

Cited by 12 | Viewed by 4518

Abstract

Endocrine-disrupting chemicals (EDCs) belong to a heterogeneous class of environmental pollutants widely diffused in different aquatic and terrestrial habitats. This implies that humans and animals are continuously exposed to EDCs from different matrices and sources. Moreover, pollution derived from anthropic and industrial activities leads to combined exposure to substances with multiple mechanisms of action on the endocrine system and correlated cell and tissue targets. For this reason, specific organs, such as the prostate gland, which physiologically are under the control of hormones like androgens and estrogens, are particularly sensitive to EDC stimulation. It is now well known that an imbalance in hormonal regulation can cause the onset of various prostate diseases, from benign prostate hyperplasia to prostate cancer. In this review, starting with the description of normal prostate gland anatomy and embryology, we summarize recent studies reporting on how the multiple and simultaneous exposure to estrogenic and anti-androgenic compounds belonging to EDCs are responsible for an increase in prostate disease incidence in the human population. Full article

(This article belongs to the Special Issue Endocrine Disruptor Chemicals and Estrogenic Activity in the Context of Health Risk Assessment)

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